Prevention of disease in humans and animals is often aided by immunizing a population of such subjects to enable the subjects' immune system to respond to the antigenic components of the pathogenic system. Though such immune stimulation or vaccination therapies have been in use for hundreds of years, pathogenic agents continue cause worldwide economic losses and much loss of life for humans and animals. For example, influenza epidemics continue to be a major disease burden in both animals and humans, with approximately 5-15% of the human population infected on an annual basis. Severe influenza disease is estimated to affect 3-5 million people worldwide, and is associated with 250,000 500,000 deaths annually. Despite efforts to curtail the emergence of novel pandemic influenza strains, an influenza virus of swine origin was responsible for a pandemic of influenza in 2009. Vaccination provides an effective means for control of influenza and it is considered the first line of defense against it. Human influenza vaccines are produced as either split virion inactivated (killed vaccines, KV) or live attenuated vaccines (LAIV). These vaccines are reformulated every year due to the virus' ability to undergo antigenic drift and escape the immunological pressure developed against previous strains.
Manufacture of vaccines or immune therapeutics is often limited by the need to grow pathogenic agents in in vitro cultures that are not ideal for the reproduction of the pathogenic agent. For example, a major drawback in the preparation of LAIV and KV influenza vaccines is that production relies on a time-consuming process of growing the viruses in eggs or tissue culture cells. Additionally, since most human influenza strains grow poorly in these systems, vaccine strains are produced from reassortants that generally carry the surface gene segments from the candidate virus and other segments from a high growth donor virus. Reverse genetics (RG) has improved the ability to generate such high growth reassortants (Neuman et al. Virology 287:243-250 (2001), Maassab et al. Rev Med Virol 9:237-244 (1999); however, growing influenza viruses in eggs or tissue culture may result in adaptive changes on the viral surface proteins resulting in antigenic mismatch. LAIV vaccines have an advantage over KV vaccines since they produce broader responses by stimulating both the humoral and the T-cell arms of the immune system (Ambrose et al. Inf Other Resp Viruses 2:193-202 (2008), Wareing et al. Vaccine 19:3320-3330 (2001)).
The 2009 pandemic H1N1 virus (pH1N1) highlighted the fact that these traditional vaccine production systems are too slow to significantly ameliorate or alter the impact of a pandemic given that the initial pH1N1 vaccine candidates were not well suited for growth in eggs (Chen et al. Journ of Infec Dis 203:930-936 (2011)). Furthermore, LAIV vaccines are not as effective in children under 2 or the elderly, which represent the groups at high risk of influenza infections. People with egg allergies cannot use egg-grown virus vaccines. Alternatively, egg-free influenza vaccine strategies have been investigated including recombinant viral proteins, recombinant viruses, and virus-like particles (VLPs) (Sedova et al. Recom Influenza Vaccines Acta Naturae 4:17-27 (2012)). FLUBLOK™, a baculovirus-based recombinant hemagglutinin influenza vaccine, is the only influenza vaccine approved for human use that does not rely on traditional production systems, but it must also undergo reformulation as a result of antigenic drift.
What is needed are methods and compositions for stimulating the immune system of a subject, such as by vaccine methods, wherein the antigenic composition or vaccine, does not need to be manufactured in tissue culture conditions, but instead, the vaccine composition is produced in the subject's body directly. What is needed are compositions and methods of treatment for reduction of infection by vaccination comprising vectors comprising polynucleotides that express pathogenic or oncogenic antigens that stimulate the immune system of a subject to whom the vector is provided.